At present, ultrasonic imaging is an imaging technique the most frequently used for clinical diagnosis. It is attracting a lot of attentions owing to many advantages including low cost, easiness of diagnosis, non-invasiveness, low risk and possibility of direct real-time imaging. Basically, ultrasonic imaging is based on the analysis of sound wave signals obtained by reflecting or scattering high-frequency sound from tissues. Various contrast agents for ultrasonic imaging have been developed to obtain more improved images and they are used for diverse biomedical purposes.
Most of the contrast agents for ultrasonic imaging are substances that generate microbubbles. The microbubble contrast agent consists of a gas included therein and an outer coat material. The microbubbles vibrate at the sound wavelength to generate enhanced ultrasound wave signals as compared to the surrounding region. However, they are not suitable for wide applications owing to very short circulation time of about several minutes and poor tissue permeation. These shortcomings result from the micro size of the contrast agents for ultrasonic imaging, which is too large to pass through the many biological barriers existing in organs and capillary vessels.
Recently, nanoparticles have emerged as a promising platform for biomedical imaging and drug delivery. Nanoparticles can circulate in the bloodstream stably for a long time and can be accumulated in angiogenic disease sites such as tumors by penetrating the newly formed blood vessels. This phenomenon, called the enhanced permeation and retention (EPR) effect, is the main advantage of nanomaterials for tumor targeting, particularly in intravenous injection. The target-specific accumulation of nanoparticles is useful both in imaging and drug delivery. Especially, multifunctional nanoparticles allow diagnosis and therapy at the same time, and this is called ‘theragnosis’. Although theragnosis is expected to provide more improved therapy clinically, nanobubbles are hardly used in ultrasonic imaging since they fail to generate ultrasound wave signals of sufficient intensity unlike the microbubbles even when the composition is similar. That is to say, although the nano size is favorable in terms of long-term circulation and accumulation in target tissues, it is disadvantageous in terms of generation of ultrasound wave signals. This is an important dilemma in the development of contrast agents for ultrasonic imaging.
In this regard, the inventors of the present disclosure have recently a new type of contrast agent for ultrasonic imaging based on a polycarbonate that generates a gas. This contrast agent is degraded in an aqueous condition to generate carbon dioxide bubbles. The generated bubbles can successfully generate ultrasound wave signals at sound wavelength like the commercially available microbubble-type contrast agents for ultrasonic imaging. The particles exhibit continuous generation of gas, thus enabling stable ultrasonic imaging for a long time. In addition, the inventors of the present disclosure have demonstrated that the amount and duration of generated carbon dioxide gas are mainly determined by contact with water and they can be adequately controlled through structural modification of particles (see Korean Patent Application No. 2009-100417).